Chemotherapy is an important treatment for ovarian cancer. However, conventional chemotherapy has inevitable drawbacks due to side effects from nonspecific biodistribution of the chemotherapeutic drugs. To solve such problem, targeted delivery approaches were developed. The targeted delivery approaches combine drug carriers with the targeting system and can preferentially bring drugs to the targeted sites. Follicle-stimulating hormone receptor (FSHR) is an ovarian cancer–specific receptor. By using a peptide derived from FSH (amino acids 33–53 of the FSH β chain, named as FSH33), we developed a conjugated nanoparticle, FSH33-NP, to target FSHR in ovarian cancer. FSH33-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. Then, the antitumor efficiency of paclitaxel (PTX)-loaded FSH33-NP (FSH33-NP-PTX) was determined. FSH33-NP-PTX displayed stronger antiproliferation and antitumor effects compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) both in vitro and in vivo. In summary, this novel FSH33-NP delivery system showed very high selectivity and efficacy for FSHR-expressing tumor tissues. Therefore, it has good potential to become a new therapeutic approach for patients with ovarian cancer. [Cancer Res 2009;69(16):6506–14]